OP0285 VOCLOSPORIN IS EFFECTIVE IN ACHIEVING PROTEINURIA TREATMENT TARGETS IN LUPUS NEPHRITIS DEFINED BY EULAR/ERA RECOMMENDATIONS
Authors: H. J. Anders, R. Federico, S. Randhawa, H. Leher
Journal: Annals of the Rheumatic Diseases (2022)

Background The novel calcineurin inhibitor voclosporin was approved in 2021 for the treatment of adult patients with active lupus nephritis (LN) in combination with background immunotherapy. Voclosporin has a favorable metabolic profile and a consistent dose-concentration relationship, eliminating the need for therapeutic drug monitoring. The Phase 2 AURA-LV and Phase 3 AURORA 1 studies demonstrated that the addition of voclosporin to mycophenolate mofetil (MMF) and low-dose steroids led to significantly higher complete renal response rates in AURA-LV at 24 weeks (32.6% vs 19.3%; odds ratio [OR] 2.03; p=0.046) and in AURORA 1 at 52 weeks (40.8% vs 22.5%; OR 2.65; p&lt;0.0001) of treatment in patients with LN. Objectives The European League Against Rheumatism and European Renal Association (EULAR/ERA) published updated treatment recommendations for LN with targeted reductions in proteinuria over the course of the first year of therapeutic intervention. 1 Here we report on a post-hoc analysis of pooled data from the similarly designed 48-week AURA-LV and 52-week AURORA 1 studies based on these updated response criteria. Methods AURA-LV and AURORA 1 enrolled patients with biopsy-proven active lupus nephritis (Class III, IV, or V ± III/IV) and proteinuria ≥1.5 mg/mg (≥2 mg/mg for Class V). Pooled data included 268 patients in the voclosporin (23.7 mg BID) group and 266 patients in the control group, with all patients receiving MMF (target dose 1 g BID) and low-dose steroids (target dose 2.5 mg/day by week 16 according to protocol-defined steroid taper). We assessed the following EULAR/ERA treatment targets: ≥25% reduction in urine protein creatinine ratio (UPCR) by 3 months, ≥50% reduction in UPCR by 6 months, UPCR ≤0.7 mg/mg by 12 months, and steroid dose ≤7.5 mg/day by 3, 6, and 12 months. Results Within the first 3 months of treatment, 78.4% of patients in the voclosporin group and 62.4% of patients in the control group achieved ≥25% reduction in UPCR (odds ratio [OR] 2.25; 95% confidence interval [CI] 1.52, 3.33; p&lt;0.0001). The percentage of patients achieving a reduction of ≥50% in UPCR by 6 months was also significantly greater in the voclosporin group compared to control (66.0% vs 47.0%, respectively; OR 2.24; CI 1.57, 3.21; p&lt;0.0001). After 12 months of treatment, 52.6% and 33.1% of patients receiving voclosporin and control, respectively, had achieved a UPCR ≤0.7 mg/mg (OR 2.52; CI 1.75, 3.63; p&lt;0.0001). Given the protocol-defined steroid taper, at both 3 and 6 months, a similar proportion (&gt;90%) of patients in both groups had achieved the recommended steroid dose, with 89.6% and 82.8% in the voclosporin and control groups, respectively, on the recommended dose at 12 months. The proportion of patients meeting all three UPCR targets during the one-year study period and having a steroid dose ≤7.5 mg/day at 12 months was 37.3% in the voclosporin group and 23.3% in the control group (OR 2.11; CI 1.43, 3.10; p=0.0001). Conclusion The addition of voclosporin to a background regimen of MMF and low-dose steroids in patients with LN significantly increased the likelihood of achieving the 3-, 6-, and 12-month UPCR targets of therapy recommended by EULAR/ERA. References [1]Fanouriakis, A. et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA–EDTA) recommendations for the management of lupus nephritis. Ann. Rheum. Dis. 79, 713–723 (2020). Figure 1. Integrated AURA-LV and AURORA 1 Analysis on the Achievement of UPCR Treatment Targets and Use of Low-Dose Steroids per EULAR/ERA Lupus Nephritis Recommendations Disclosure of Interests Hans-Joachim Anders: None declared, Ray Federico Shareholder of: Aurinia Pharmaceuticals Inc., Employee of: Aurinia Pharmaceuticals Inc., Simrat Randhawa Shareholder of: Aurinia Pharmaceuticals Inc., Employee of: Aurinia Pharmaceuticals Inc., Henry Leher Shareholder of: Aurinia Pharmaceutical Inc., Employee of: Aurinia Pharmaceutical Inc.